Protective effect of new adenosine analog B2 against serum deprivation-induced PC12 cell injury.
- Author:
Jing SUN
1
;
Min LI
;
Rui-xia KANG
;
Jian-gong SHI
;
Jian-jun ZHANG
Author Information
1. Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Adenosine;
analogs & derivatives;
metabolism;
pharmacology;
Adenosine A2 Receptor Antagonists;
pharmacology;
Animals;
Cell Survival;
drug effects;
Corpus Striatum;
metabolism;
Culture Media, Serum-Free;
Female;
Male;
PC12 Cells;
Pyrimidines;
pharmacology;
Rats;
Rats, Wistar;
Reactive Oxygen Species;
metabolism;
Receptor, Adenosine A2A;
metabolism;
Triazoles;
pharmacology
- From:
Acta Pharmaceutica Sinica
2011;46(10):1199-1203
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the effect of compound B2 on the damage of PC12 cells induced by serum deprivation and to explore its related mechanisms. The binding characteristics of B2 to rat striatum adenosine A2A receptor was studied by radioligand 3H-MSX-2 binding assay. Cell viability was detected by MTT assay. ROS formation was measured after DCFDA fluorescent staining. B2 has affinity to rat adenosine A2A receptor (K1 = 0.37 micromol x L(-1)). B2 remarkably increased PC12 cell survival rate in serum deprivation-induced PC12 cells. The percentage of serum deprivation-induced death of PC12 was 49.6%, and the treatment of B2 (0.1-100 micromol x L(-1)) increased the cell viability to 63.3%, 74.9%, 86.3% and 88.1%, respectively. Adenosine A2A receptor antagonist SCH 58261 could significantly block the protective effect of B2. The cell viability with 0.1 micromol x L(-1) SCH 58261 decreased by 16.1%, 24.0% and 19.8%, in the presence of B2 (0.1-10 micromol x L(-1)). Serum deprivation-induced ROS formation was 3.5 times more than that of control group, and treatment with B2 significantly and dose-dependently inhibited ROS over-formation. The protective effect of B2 may be related with adenosine A2A receptor. Decrease of serum-deprivation induced ROS formation may also be one of the mechanisms.
